BACKGROUND: Posterior capsule opacification (PCO) represents a major challenge in the postoperative management of cataract patients. Spreading, migration and contraction of residual human lens epithelial cells play a pivotal role in the pathogenesis of PCO. Therefore, we analyzed the effect of the alkylphosphocholine (APC) erufosine on these cellular features as well as on PI3K/Akt, a crucial pathway in PCO pathogenesis. METHODS: Human lens epithelial cells were cultured under standard cell culture conditions. Cell spreading was analyzed on fibronectin-coated wells and chemokinetic migration was assessed by time-lapse microscopy. For evaluation of cell-mediated collagen matrix contraction, the cells were seeded into collagen gels and incubated with an APC in different non-toxic concentrations before the surface area was measured on day 6. The activity of PI3K/Akt was assessed by an ELISA kit after incubation of the cells with different APC concentrations. RESULTS: Human lens epithelial cell spreading and migration were attenuated by APCs as follows: 7 % spreading, 48 % migration (0.1 μM APC), and 32 % spreading, 68 % migration (1.0 μM APC). APC concentrations of 0.1 μM reduced collagen gel diameter by 5 %, and 1.0 μM by less than 1 %, compared to untreated, cell-populated gels that resulted in a cell diameter contraction of 36 %. PI3K was downregulated in a concentration-dependent manner. CONCLUSIONS: The crucial cellular features of PCO pathogenesis are attenuated by the APC erufosine via downregulation of the PI3K pathway. Thus, erufosine might become a valuable tool for pharmacologic PCO prophylaxis in the future.
BACKGROUND: Posterior capsule opacification (PCO) represents a major challenge in the postoperative management of cataractpatients. Spreading, migration and contraction of residual human lens epithelial cells play a pivotal role in the pathogenesis of PCO. Therefore, we analyzed the effect of the alkylphosphocholine (APC) erufosine on these cellular features as well as on PI3K/Akt, a crucial pathway in PCO pathogenesis. METHODS:Human lens epithelial cells were cultured under standard cell culture conditions. Cell spreading was analyzed on fibronectin-coated wells and chemokinetic migration was assessed by time-lapse microscopy. For evaluation of cell-mediated collagen matrix contraction, the cells were seeded into collagen gels and incubated with an APC in different non-toxic concentrations before the surface area was measured on day 6. The activity of PI3K/Akt was assessed by an ELISA kit after incubation of the cells with different APC concentrations. RESULTS:Human lens epithelial cell spreading and migration were attenuated by APCs as follows: 7 % spreading, 48 % migration (0.1 μM APC), and 32 % spreading, 68 % migration (1.0 μM APC). APC concentrations of 0.1 μM reduced collagen gel diameter by 5 %, and 1.0 μM by less than 1 %, compared to untreated, cell-populated gels that resulted in a cell diameter contraction of 36 %. PI3K was downregulated in a concentration-dependent manner. CONCLUSIONS: The crucial cellular features of PCO pathogenesis are attenuated by the APC erufosine via downregulation of the PI3K pathway. Thus, erufosine might become a valuable tool for pharmacologic PCO prophylaxis in the future.
Authors: D J Apple; Q Peng; N Visessook; L Werner; S K Pandey; M Escobar-Gomez; J Ram; G U Auffarth Journal: Ophthalmology Date: 2001-03 Impact factor: 12.079
Authors: Frank Schuettauf; Kirsten H Eibl; Sebastian Thaler; Kei Shinoda; Robert Rejdak; C Albrecht May; Georgios Blatsios; Ulrich Welge-Lussen Journal: Curr Eye Res Date: 2005-09 Impact factor: 2.424
Authors: Vania A Figueroa; Oscar Jara; Carolina A Oliva; Marcelo Ezquer; Fernando Ezquer; Mauricio A Retamal; Agustín D Martínez; Guillermo A Altenberg; Aníbal A Vargas Journal: Front Physiol Date: 2020-01-20 Impact factor: 4.566